Complex molecule synthesis offers an unparalleled opportunity to develop and demonstrate new synthetic chemical technologies. Fundamental studies into a new reaction or expansion of an existing molecular transformation can increase the efficiency of the synthesis of a target molecule. Specifically, this proposal is focused on developing rapid and efficient access to complex pyrrolidine heterocycles. A research criterion is to exclude acutely toxic reagents, which will allow for straightforward application to the manufacturing of modern Pharmaceuticals in accord with the FDA's current Good Manufacturing Practices (cGMP). Daphniyunnine D was recently isolated from the stems and leaves of Daphniphyllum yunnanense and constitutes 0.0035% of the dry weight plant mass. This alkaloid shows activity against two tumor cell lines, P-388 and A-549, with IC50 values of 3.0 and 0.6 ?M, respectively. In order to secure sufficient quantities and fully determine the therapeutic potential of daphniyunnine D, a synthetic effort is required. A primary objective of this proposal will be the development of a new class of intramolecular azomethine ylide cyclizations and the demonstration of this reaction in the total synthesis of the complex hexacyclic alkaloid daphniyunnine D. The method for generating the requisite azomethine ylide requires a judicious choice. This choice will be discussed in detail along with the development of this Type III intramolecular azomethine ylide cyclization. Different reaction conditions designed to obtain the necessary reactivity without compromising the stability of the azomethine ylide will be discussed. This high complexity-generating step will allow access to complex derivatives of the coveted pyrrolidine heterocycle and complete the molecular skeleton of daphniyunnine D. Finally, this synthesis of daphniyunnine D will investigate a rational approach for controlling diastereoselectivity in the Pauson-Khand cyclization. [unreadable] [unreadable] [unreadable]